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The Jagged-1/Notch-1/Hes-1 Pathway Is Involved in Intestinal Adaptation in a Massive Small Bowel Resection Rat Model

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Abstract

Background

Notch signaling is required for the maintenance of intestinal epithelial proliferation. Dysfunction of this signaling pathway is associated with the loss of proliferated crypt epithelial cells.

Aim

The aim of this study was to investigate the role of Notch signaling in small bowel resection (SBR)-associated crypt epithelial cell proliferation.

Methods

Male Sprague–Dawley rats were subjected to sham operation (bowel transection and reanastomosis) or 70 % mid-SBR. Intestinal tissue samples were collected at 0.5, 1, 6, 12, 24, 72, and 168 h after operation. The expression of Notch pathway mRNAs and proteins was analyzed using RT-PCR and Western blot. The expression of the Notch pathway proteins Jagged-1, NICD and Hes-1 was also determined through immunohistochemical staining using day 3 postoperative intestinal tissues. The degree of crypt epithelial cell proliferation was evaluated using the immunohistochemical staining of proliferating cell nuclear antigen (PCNA). Furthermore, IEC-6 cells were used to examine the function of the Jagged-1 signaling system.

Results

SBR led to increased crypt epithelial cell proliferation and increased expression of Jagged-1 and Hes-1 mRNA and protein along with cleaved Notch-1. Immunohistochemical staining showed that Jagged-1, cleaved Notch-1 and Hes-1 colocalized in the same proliferated crypt epithelial cell population. Recombinant Jagged-1 significantly stimulated the proliferation of IEC-6 cells. Transient upregulation of Jagged-2 expression was found 1 h after SBR, and it was accompanied by cleaved Notch-1 and Hes-1 upregulation.

Conclusion

The Jagged-1/Notch-1/Hes-1 signaling pathway is involved in intestinal adaptation through increasing crypt epithelial cell proliferation.

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Acknowledgments

This research was supported by grants from the National Natural Science Foundation of China (Nos. 81020108023, 81272078,81200288) and the Chongqing Science and Technology Commission International Key Collaboration Project (CSTC 201110008).

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Authors and Affiliations

  1. Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China

    Guoqing Chen, Lihua Sun, Min Yu, Dan Meng, Wensheng Wang, Yang Yang & Hua Yang

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  1. Guoqing Chen
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  2. Lihua Sun
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  3. Min Yu
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  4. Dan Meng
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  5. Wensheng Wang
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  6. Yang Yang
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  7. Hua Yang
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Correspondence to Hua Yang.

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Chen, G., Sun, L., Yu, M. et al. The Jagged-1/Notch-1/Hes-1 Pathway Is Involved in Intestinal Adaptation in a Massive Small Bowel Resection Rat Model. Dig Dis Sci 58, 2478–2486 (2013). https://doi.org/10.1007/s10620-013-2680-3

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  • DOI: https://doi.org/10.1007/s10620-013-2680-3

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